Scientists have developed a new method that uses nanoparticles for delivering drugs to treat traumatic brain injuries that are commonly caused by a violent blow, fall, or a crash to the head.

Dubbed as the ‘silent epidemic,’ traumatic brain injury or TBI kills 150 Americans every day, according to the CDC. In other cases, it causes a lasting neurological impact that leads to memory disturbances, behavioral changes, and speech irregularities. Scientists have previously explored treatments for TBI but haven’t been successful mainly because the blood-brain barrier (BBB) is restrictive and doesn’t allow just any molecule into the brain.

The new proof-of-concept approach, described in a paper published January 1st in Science Advances, aims to overcome this barrier by using nanoparticles which are increasingly used as drug delivery agents. These particles can be modified to increase their therapeutic effects and can be specifically targeted to deliver drugs.

“It’s very difficult to get both small and large molecule therapeutic agents delivered across the BBB,” said Nitin Joshi, corresponding author, and bioengineer at Brigham and Women’s Hospital. “Our solution was to encapsulate therapeutic agents into biocompatible nanoparticles with precisely engineered surface properties that would enable their therapeutically effective transport into the brain, independent of the state of the BBB.”

One among these therapeutic agents is the small interfering RNA or siRNA, a short nucleic acid strand that controls how genes function. The team tested five different molecules and engineered a nanoparticle that could shuttle siRNA across the blood-brain barrier without any hindrance. Then, they tested this nanoparticle on healthy and brain-injured mice.

Then, the scientists analyzed whether the nanoparticles carried the siRNA all the way inside the neural cells so that the molecule could act as a therapeutic agent by silencing certain genes.

“To be able to deliver agents across the BBB in the absence of inflammation has been somewhat of a holy grail in the field,” said Jeffrey Karp, a biomedical engineer, professor at Harvard Medical School, and co-senior author of the study. “Our radically simple approach is applicable to many neurological disorders where delivery of therapeutic agents to the brain is desired.”

The researchers also investigated whether the synthesized nanoparticles could deliver siRNA to suppress tau proteins that are found mostly in neurons. These proteins clump together in the brains of people with encephalopathy and Alzheimer’s — diseases that eventually arise after a traumatic brain injury. They found that tau proteins were 70% less expressed in mice treated with tau siRNA.

“The technology developed for this publication could allow for the delivery of [a] large number of diverse drugs, including antibiotics, antineoplastic agents, and neuropeptides,” said Rebekah Mannix, co-senior author, associate professor at Harvard Medical School. “This could be a game-changer for many diseases that manifest in the central nervous system.”

However, a number of questions still need to be answered about what other pathways lead to behavioral changes in TBI. Moving forward, the researchers plan to look at other biological pathways in the brain using this delivery platform.